Table 3.1-2. Clinically significant interactions with VKAs (acenocoumarol, warfarin)

Drug/substance class

Effects on VKA anticoagulant activity




A: Ciprofloxacin, erythromycin, fluconazole, isoniazid (600 mg/d), sulfamethoxazole/trimethoprim, metronidazole, miconazole,a voriconazole

B: Amoxicillin/clavulanic acid, azithromycin, itraconazole, ketoconazole, clarithromycin, levofloxacin, ritonavir, tetracycline

A: Griseofulvin, nafcillin, ribavirin, rifampicin

B: Dicloxacillin, ritonavir

Cardiovascular drugs

A: Amiodarone, diltiazem, fenofibrate, clofibrate, propafenone, propranolol, sulfinpyrazoneb

B: Quinidine, fluvastatin, acetylsalicylic acid, ropinirole, simvastatin

A: Cholestyramine

B: Bosentan, spironolactone

Analgesics, anti-inflammatory and immunomodulatory drugs

A: Phenylbutazone

B: Interferon, acetylsalicylic acid, acetaminophen, tramadol

A: Mesalamine

B: Azathioprine

Central nervous system drugs

A: Alcohol (in patients with coexisting liver disease), citalopram, entacapone, sertraline

B: Disulfiram, chloral hydrate, fluvoxamine, phenytoin,c tricyclic antidepressants (amitriptyline, clomipramine), benzodiazepines

A: Barbiturates, carbamazepine

B: Chlordiazepoxide

Gastrointestinal drugs and foods

A: Cimetidine,c mango, fish oil, omeprazole

B: Grapefruit juice, prokinetic agents (particularly cisapride)

A: Avocado (in large quantities), foods rich in vitamin K1,d enteral nutrition

B: Soy milk, sucralfate

Other drugs

A: Anabolic steroids, zileuton, zafirlukast

B: Fluorouracil, gemcitabine, levamisole with fluorouracil, paclitaxel, tamoxifen, tolterodine, thiamazole, L-thyroxine

A: Mercaptopurine

B: Raloxifene, multivitamin supplements, influenza vaccines, chelating agents

A, causation is highly probable. B, causation is probable.

a Oral topical gel and vaginal suppositories.

b Initial potentiation followed by inhibition.

c Applies to warfarin.

d For instance, kale, spinach, different varieties of cabbage (Chinese, mustard greens, sauerkraut), beet leaves, Brussels sprouts, broccoli, dandelion (leaves), various types of lettuce, green parsley, asparagus, onions (spring onions and shallots), chicory. Frozen foods are usually richer in vitamin K than fresh foods. One cup (~250 mL) of the foods listed in the table contains ≥80 microg of vitamin K1 (daily requirement, 80-120 microg).

Adapted from Arch Intern Med. 2005;165(10):1095-106.

VKA, vitamin K antagonist.